Regulation of GATA-3 expression during CD4 lineage differentiation

• Published in: The Journal of immunology (1950) Vol. 186; no. 7; pp. 3892 - 3898
• Main Authors: Gimferrer, Idoia, Hu, Taishan, Simmons, Amie, Wang, Chi, Souabni, Abdallah, Busslinger, Meinrad, Bender, Timothy P, Hernandez-Hoyos, Gabriela, Alberola-Ila, José
• Format: Journal Article
• Language: English
• Published: United States 01.04.2011
• Subjects: Animals; Calcineurin - physiology; CD4-Positive T-Lymphocytes - cytology; CD4-Positive T-Lymphocytes - immunology; CD4-Positive T-Lymphocytes - metabolism; Cell Differentiation - genetics; Cell Differentiation - immunology; Cell Lineage - genetics; Cell Lineage - immunology; DNA-Binding Proteins - physiology; GATA3 Transcription Factor - biosynthesis; GATA3 Transcription Factor - genetics; GATA3 Transcription Factor - metabolism; Gene Expression Regulation - immunology; Gene Knock-In Techniques; HEK293 Cells; Humans; Mice; Mice, Inbred C57BL; Mice, Knockout; Mice, Transgenic; Proto-Oncogene Proteins c-myb - physiology; ras Proteins - physiology; Signal Transduction - genetics; Signal Transduction - immunology; Transcription Factors - physiology
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.1003505

GATA-3 is necessary for the development of MHC class II-restricted CD4 T cells, and its expression is increased during positive selection of these cells. TCR signals drive this upregulation, but the signaling pathways that control this process are not well understood. Using genetic and pharmacological approaches, we show that GATA-3 upregulation during thymocyte-positive selection is the result of additive inputs from the Ras/MAPK and calcineurin pathways. This upregulation requires the presence of the transcription factor c-Myb. Furthermore, we show that TH-POK can also upregulate GATA-3 in double-positive thymocytes, suggesting the existence of a positive feedback loop that contributes to lock in the initial commitment to the CD4 lineage during differentiation.